Is Exercise during Pregnancy a Risk for Gestational Age and Preterm Delivery? Systematic Review and Meta-Analysis

Traditionally, one of the primary concerns regarding exercise during pregnancy has been the potential of reducing gestational age and increasing the likelihood of preterm delivery. The aim of this study was to perform a systematic review about the effects of physical activity (PA) during pregnancy on gestational age and preterm delivery. A systematic review and two meta-analyses were performed (Registration No. CRD42022370770). Data sources from online databases were searched up to November 2022. The review exclusively included studies involving pregnant populations and interventions consisting of PA implemented during pregnancy. The primary outcomes analysed were gestational age, measured in weeks, and the occurrence of preterm deliveries. A total of 57 studies were analysed through two independent meta-analyses for the first one, no association was found between moderate exercise during pregnancy and gestational age (Z = 0.45, p = 0.65, ES = 0.08, 95% CI = −0.06−0.04, I2 = 42%, P heterogeneity = 0.001), showing the exercise group had a higher gestational age. In addition, no differences were found between groups in terms of number of preterm deliveries (RR = 0.96, (95% CI = 0.77–1.21, Z = 0.33, p = 0.74; ES = 0.07; I2 = 31%, P heterogeneity = 0.05)). The findings of this study indicate that there is no association between exercise during pregnancy and reduced gestational age or increased risk of preterm delivery in healthy pregnancies.


Introduction
The intricate process of pregnancy and childbirth plays a crucial role in shaping the long-term health outcomes for both the mother and the child. Spanning over several months, it involves substantial modifications in nearly all of a woman's bodily systems to support the growth and development of the foetus. Therefore, it is imperative to ensure the optimal functioning of all maternal physiological, mental, and emotional mechanisms that facilitate foetal growth and development. Any complications arising within these domains of health may contribute to pathologies and complications that adversely affect the well-being of both the mother and the newborn [1,2].
The numerous demands imposed by pregnancy transform the process of gestation and childbirth into a formidable challenge that women must navigate throughout the forty weeks of gestational age. Their goal is to avert pathologies and adverse outcomes, such as preterm delivery, which can give rise to significant associated complications [3,4].
Premature birth refers to the condition where a baby is born before the completion of a full-term pregnancy, which lasts approximately 40 weeks. Preterm birth, on the other hand, occurs when delivery takes place prior to the 37th week of pregnancy. Premature babies often encounter significant health challenges, particularly when born at earlier 2 of 16 stages of gestation. The nature and severity of these problems can vary, with a higher risk of associated health complications observed as the gestational age decreases [5]. In this intricate scenario, it is crucial for pregnant women to prioritize the well-being of all aspects of their body, encompassing not only physiological factors but also mental and emotional aspects [6].
In light of scientific evidence, it is well-established that unhealthy lifestyles have negative implications for pregnancy outcomes. Engaging in an unhealthy lifestyle during pregnancy heightens the risk of chronic diseases [7]. Moreover, the escalating epidemic of obesity and sedentary habits significantly impacts pregnancy and childbirth, with enduring adverse consequences [8]. The scientific literature highlights the substantial benefits derived from various forms of physical activity (PA) in terms of pregnancy outcomes and overall health and well-being [9,10]. Nevertheless, the impact of PA during pregnancy on gestational age and preterm delivery has not been extensively investigated, leaving significant scientific gaps [11].
Achieving an optimal gestational age and preventing a preterm delivery are two crucial factors that significantly impact the well-being of both the mother and child during the pre-, peri-, and postnatal periods. Traditionally and historically, physical exercise during pregnancy has been inaccurately perceived as a challenging factor for both gestational age and preterm birth.
PA has become an integral component for diverse populations, including pregnant women. Many studies have confirmed the benefits of PA on different maternal, foetal, and newborn outcomes. Nevertheless, the impact of various types of PA on gestational age and preterm delivery has been inadequately examined through systematic reviews, resulting in a significant knowledge gap in this scientific domain. Through a rigorous analysis of the recent literature, it is evident that only a few studies with high reliability, such as systematic reviews with meta-analyses, have been conducted. Thus, studies with a rigorous scientific methodology and guaranteed reliability are essential to generate new evidence on this issue.
In this sense, in the recent scientific literature, only one systematic review study [12] has specifically investigated the effects of gestational PA on preterm delivery. The objective of this systematic review and meta-analysis is to examine the current scientific evidence concerning the effects of PA during pregnancy on gestational age and the occurrence of preterm delivery.

Materials and Methods
This study was developed following the Preferred Reporting Items for Systematic reviews (PRISMA) guidelines [13] and registered with the International Prospective Register of Systematics reviews (PROSPERO, registration No. CRD42022370770). Population, Intervention, Comparison, Outcomes and Study design framework (PICOS) was used to analyse the searching sources included in this research [14].

Population
Pregnant women without any obstetrical relative (e.g., gestational hypertension, malnutrition, or moderate cardiovascular disease) or absolute (e.g., premature labour, preeclampsia, or incompetent cervix) contraindications, participating in a PA programme during pregnancy were chosen.

Intervention
The intervention characteristics analysed were: (a) weekly frequency of PA sessions; (b) intensity: all studies included had a moderate intensity of load, using 55-65% of the maximum maternal heart rate or the perception of effort (range 12-14 of the Borg Scale); (c) duration of the PA program; (d) type of PA (e.g., yoga, Pilates, aerobic, strength, or pelvic floor training); (e) supervision or not of the PA program; (f) time duration of the sessions, as shown in Table 1.

Comparison
Women who engaged in an exercise or PA program during pregnancy were compared with those who did not participate in such a program. Intervention characteristics were retrieved and compared as shown in Table 1.

Outcomes
The gestational age (measured in weeks) and the preterm deliveries were the target outcome. Eligible articles for our review included studies that had a quantifiable PA or exercise intervention (excluding the articles with only advice to have an active pregnancy or those having a measurable PA questionnaire but without an exercise intervention), with gestational age or preterm delivery as outcomes, and with the characteristics of the PA or exercise program provided. This process is detailed in Figure 1.

Study Design and Selection Process
The primary outcomes were gestational age and preterm birth. Studies reporting either of them were included in the review. Firstly, two reviewers (M.S.-P. and D.Z.) screened independently the studies retrieved in the search achieving a complete consensus in the decision about the eligible studies. In a second stage, two reviewers (M.S.-P. and C.S.) performed the data extraction from the included studies. In case of doubt at that stage, they consulted with the rest of the authors until an agreement on the appropriate manner to report the information from the study was reached. In cases where both gestational age and preterm delivery were reported in the same study, both measures were separately included in the meta-analysis. Additionally, to check the effects of each intervention on maternal health, other outcomes were examined (but not included in the meta-analyses) as secondary outcomes, such as physiologic, sociodemographic, and delivery outcomes. From each chosen study, we extracted the author(s), publication year, country in which the study was developed, type of study design, number of participants, characteristics of the intervention program, and variables analysed (primary and secondary) ( Table 1).

Statistical Analysis, Quality of Evidence Assessment, and Risk of Bias
As mentioned earlier, two separate meta-analyses were performed. For the first metaanalysis including the studies reporting gestational age as a continuous variable, the overall confidence interval (CI) was calculated using the standardized mean difference [15]. For the second meta-analysis, the dependent variable was the ratio of preterm deliveries in each study, and it was expressed as a categorical variable (yes/no). In that case, the number of events present in each study group and its relative risk (RR) were recorded, and the total sum of the RR was calculated using a random-effects model [16]. In both analyses, each study had a relative weight assignment corresponding to its sample size number, which contributed to the entire analysis, establishing the compensated average. The I2 statistic was used to quantify the heterogeneity present in the results due to the different interventions and designs of each article, indicating the variability of the effect of each intervention, and whether it was random or not. The following considerations were used: low heterogeneity = 25%; moderate heterogeneity = 50%; and high heteroge-

Statistical Analysis, Quality of Evidence Assessment, and Risk of Bias
As mentioned earlier, two separate meta-analyses were performed. For the first metaanalysis including the studies reporting gestational age as a continuous variable, the overall confidence interval (CI) was calculated using the standardized mean difference [15]. For the second meta-analysis, the dependent variable was the ratio of preterm deliveries in each study, and it was expressed as a categorical variable (yes/no). In that case, the number of events present in each study group and its relative risk (RR) were recorded, and the total sum of the RR was calculated using a random-effects model [16]. In both analyses, each study had a relative weight assignment corresponding to its sample size number, which contributed to the entire analysis, establishing the compensated average. The I2 statistic was used to quantify the heterogeneity present in the results due to the different interventions and designs of each article, indicating the variability of the effect of each intervention, and whether it was random or not. The following considerations were used: low heterogeneity = 25%; moderate heterogeneity = 50%; and high heterogeneity = 75% [17]. Ferreira-González et al. [18] demonstrated that in the case of a high heterogeneity, one solu-tion could be to divide the studies into subgroups performed with different characteristics explaining that variability. However, for our article with limited results, we understood that presenting all articles in each analysis would provide a better approach for the study.
For the assessment of the quality of evidence for the main outcome and each study, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used, including studies rated as having a moderate or high quality [19]. To determine the potential risk of bias (with these sources: selection, performance, attrition, detection, and reporting bias), the Cochrane Handbook was followed [20]. Randomised clinical trials' evidence initially started with a "low" risk of bias (due to the theoretical study design and intervention), compared to nonrandomised interventions, and both increased or decreased its risk of bias in function of having any "high" or "low" score across bias sources. Both the quality of the study and the risk of bias analyses were performed by three of the reviewers (M.S.-P., C.S., and E.F.). It is usually in the method section in "outcomes", and they appear as "main outcomes". If main variables do not appear, they are the first. One can find it in several places. Secondary variables: the same as before but secondary.

Results
In total, 276 articles were retrieved in the first stage of the search, 184 of which were excluded because they did not meet the inclusion criteria ( Figure 1). Then, 35 articles were excluded since they were a narrative review (n = 8), a pilot study (n = 5), they did not describe the intervention protocol (n = 12), or they did not provide information regarding gestational age (n = 10). Finally, 57 studies were included in the analysis.
For the first meta-analysis, all the selected studies were included that reported gestational age (Figure 2). On the other hand, 34 of them were represented in the second meta-analysis (Figure 3). In this group, studies reporting whether the women had had a preterm delivery were included.   Regarding the type of intervention reported in the included studies (as shown in Table 1), most of them described PA sessions conducted by professionals in the field. The intervention consisted of aerobic exercise, strength exercises, or aquatic activities among others. The sessions in the studies included in the review were designed for moderate intensity and performed with a frequency of one to seven days per week, with a time duration between 15 and 75 min. The duration of each intervention oscillated between 2 and 24 weeks.
In terms of the quality of evidence assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, a total of 52 randomized controlled trials (RCTs) were analysed for the assessment of gestational age. The findings of these trials resulted in a classification of a "moderate" certainty and "critical" importance. Similarly, for the analysis of preterm delivery, 34 RCTs were evaluated, which provided a classification of a "high" certainty and "critical" importance.
Regarding the type of intervention reported in the included studies (as shown in Table 1), most of them described PA sessions conducted by professionals in the field. The intervention consisted of aerobic exercise, strength exercises, or aquatic activities among others. The sessions in the studies included in the review were designed for moderate intensity and performed with a frequency of one to seven days per week, with a time duration between 15 and 75 min. The duration of each intervention oscillated between 2 and 24 weeks.
In terms of the quality of evidence assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, a total of 52 randomized controlled trials (RCTs) were analysed for the assessment of gestational age. The findings of these trials resulted in a classification of a "moderate" certainty and "critical" importance. Similarly, for the analysis of preterm delivery, 34 RCTs were evaluated, which provided a classification of a "high" certainty and "critical" importance.

Effect of PA on Gestational Age
Fifty-two different studies were included in this analysis, comparing gestational age between women in the experimental and control groups. The results revealed there was no significant association between exercise practice during pregnancy and gestational age (Z = 0. 45 Figure 2 shows the forest plot corresponding to the present meta-analysis.

Effect of PA on the Risk of Preterm Delivery
Thirty-four studies were included in this analysis comparing the difference in the ratio of preterm deliveries between the experimental and control groups. The results revealed that there was no association between PA practice during pregnancy and preterm delivery risk. Specifically, the total compensated RR was 0.96 (95% CI = 0.77-1.21, Z = 0.33, p = 0.74: ES = 0.07), and the values for heterogeneity analysis were Chi 2 33 = 47.49 (p = 0.05), I2 = 31%). These outcomes indicate that women who exercised during pregnancy did not present a significantly greater probability of experiencing preterm delivery. Figure 3 shows the forest plot corresponding to the present meta-analysis.

Risk of Bias Assessment
Overall, the risk of bias of each article was rated as low, unclear, or as a high potential risk ( Figure 4). Reviewing the sources of bias, the articles showed mostly a low risk of bias on selection, detection, and attrition bias. Nearly a half of the studies (n = 27) presented an unclear performance risk. In this type of research (controlled trials), blinding participants is practically impossible. On the other hand, a high (n = 5) or unclear (n = 12) selection bias was reported for some studies due to the difficulty to access each protocol. Despite the high percentage of unclear risk of bias findings in the performance source, we followed Cochrane's tool considering the difficulty in these types of studies when it comes to blinding participants [20]. Despite the high risk of bias scored in the reporting source, the outcomes of interest of each article (even the inaccessibility of their protocols) could not be related to gestational age or preterm delivery. The summary of the risk of bias assessment per study is included as Supplementary Materials (File S1). no significant association between exercise practice during pregnancy and gestational age (Z = 0.45, p = 0.65; ES = 0.08; 95% CI = −0.01 [−0.06-0.04]; and the values for heterogeneity analysis were Chi 2 50 = 86.04 (p = 0.001), I2 = 42%). Figure 2 shows the forest plot corresponding to the present meta-analysis.

Effect of PA on the Risk of Preterm Delivery
Thirty-four studies were included in this analysis comparing the difference in the ratio of preterm deliveries between the experimental and control groups. The results revealed that there was no association between PA practice during pregnancy and preterm delivery risk. Specifically, the total compensated RR was 0.96 (95% CI = 0.77-1.21, Z = 0.33, p = 0.74: ES = 0.07), and the values for heterogeneity analysis were Chi 2 33 = 47.49 (p = 0.05), I2 = 31%). These outcomes indicate that women who exercised during pregnancy did not present a significantly greater probability of experiencing preterm delivery. Figure 3 shows the forest plot corresponding to the present meta-analysis.

Risk of Bias Assessment
Overall, the risk of bias of each article was rated as low, unclear, or as a high potential risk (Figure 4). Reviewing the sources of bias, the articles showed mostly a low risk of bias on selection, detection, and attrition bias. Nearly a half of the studies (n = 27) presented an unclear performance risk. In this type of research (controlled trials), blinding participants is practically impossible. On the other hand, a high (n = 5) or unclear (n = 12) selection bias was reported for some studies due to the difficulty to access each protocol. Despite the high percentage of unclear risk of bias findings in the performance source, we followed Cochrane's tool considering the difficulty in these types of studies when it comes to blinding participants [20]. Despite the high risk of bias scored in the reporting source, the outcomes of interest of each article (even the inaccessibility of their protocols) could not be related to gestational age or preterm delivery. The summary of the risk of bias assessment per study is included as Supplementary Materials (File S1).

Discussion
The objective of the present systematic review and meta-analysis was to investigate the impact of PA during pregnancy on gestational age and the occurrence of preterm delivery. By assessing the potential risks to maternal and foetal well-being associated with an integral component of a pregnant woman's daily life, namely PA, we aimed to enhance our understanding of its influence.
Our findings indicated that there were no adverse effects observed on both gestational age and the occurrence of preterm delivery. In fact, the exercise groups demonstrated a lengthened gestational age compared to the control groups, which is consistent with findings from other studies [11]. This is particularly significant because traditionally,

Discussion
The objective of the present systematic review and meta-analysis was to investigate the impact of PA during pregnancy on gestational age and the occurrence of preterm delivery. By assessing the potential risks to maternal and foetal well-being associated with an integral component of a pregnant woman's daily life, namely PA, we aimed to enhance our understanding of its influence.
Our findings indicated that there were no adverse effects observed on both gestational age and the occurrence of preterm delivery. In fact, the exercise groups demonstrated a lengthened gestational age compared to the control groups, which is consistent with findings from other studies [11]. This is particularly significant because traditionally, a major concern surrounding exercise during pregnancy has been the potential for a decreased gestational age and increased risk of preterm delivery. However, our results support the recommendation of moderate PA throughout pregnancy for pregnant women without obstetric contraindications, aligning with a substantial body of literature [78][79][80].
From an epidemiological standpoint, when examining the underlying causes of the beneficial impact of physical exercise on gestational age, we encountered ample evidence to support a causal association between unhealthy lifestyles-such as excessive maternal weight gain, obesity, and smoking-and the occurrence of preterm delivery [81][82][83].
These findings lead us to propose the concept of a comprehensive preventive effect of PA throughout pregnancy, mitigating the risk factors associated with reduced gestational age and preterm birth. This notion is supported by other studies demonstrating the potential of PA to positively impact not only physiological aspects but also mental and emotional aspects, and the overall quality of life in pregnant women [84,85].
The results of this study further validate the current recommendations of engaging in 150 min of moderate PA per week throughout pregnancy for women without obstetric contraindications [79].
While no significant limitations of the evidence or the review processes used in the current study were identified, there are two minor limitations worthy of note. The first one refers to the diversity of interventions involving PA across the included studies; the absence of standardized protocols hampers the potential of meta-analyses to their fullest extent. On the other hand, the review included both women who exercised before and women who started exercising during pregnancy. However, we believe that this variability is inherent in the nature of the intervention itself.

Conclusions
PA during pregnancy does not contribute to adverse outcomes in terms of gestational age or increase the risk of preterm delivery among healthy pregnant women.